A-T (ataxia telangiectasia) individuals frequently display gonadal atrophy, and Atm؊/؊ mice show spermatogenic failure due to arrest at prophase of meiosis I. Chromosomal movements take place during meiotic prophase, with telomeres congregating on the nuclear envelope to transiently form a cluster during the leptotene/zygotene transition (bouquet arrangement). Since the ATM protein has been implicated in telomere metabolism of somatic cells, we have set out to investigate the effects of Atm inactivation on meiotic telomere behavior. Fluorescent in situ hybridization and synaptonemal complex (SC) immunostaining of structurally preserved spermatocytes I revealed that telomere clustering occurs aberrantly in Atm ؊/؊ mice. Numerous spermatocytes of Atm ؊/؊ mice displayed locally accumulated telomeres with stretches of SC near the clustered chromosome ends. This contrasted with spermatogenesis of normal mice, where only a few leptotene/zygotene spermatocytes I with clustered telomeres were detected. Pachytene nuclei, which were much more abundant in normal mice, displayed telomeres scattered over the nuclear periphery. It appears that the timing and occurrence of chromosome polarization is altered in Atm ؊/؊ mice. When we examined telomere-nuclear matrix interactions in spermatocytes I, a significant difference was observed in the ratio of soluble versus matrixassociated telomeric DNA sequences between meiocytes of Atm ؊/؊ and control mice. We propose that the severe disruption of spermatogenesis during early prophase I in the absence of functional Atm may be partly due to altered interactions of telomeres with the nuclear matrix and distorted meiotic telomere clustering.Ataxia telangiectasia (A-T) is an autosomal recessive disorder characterized by progressive neurological degeneration, premature aging, growth retardation, specific immunodeficiencies, telangiectasia, high sensitivity to ionizing radiation, genomic instability, cancer progression, and gonadal atrophy (9, 31). Cells derived from A-T individuals exhibit a variety of abnormalities in culture such as cytoskeletal defect, hypersensitivity to ionizing radiation, and higher requirement for serum growth factors (51, 78). They also show a prominent chromatin defect at chromosome ends in the form of chromosome endto-end associations (also known as telomeric associations) seen at metaphase (38,61,63,89). Chromosome end associations correlate with genomic instability and carcinogenicity (18,61,63) and involve telomeres (48,55). Telomeres consist of repetitive (TTAGGG) DNA and proteins which protect chromosome ends from exonucleolytic attack, fusion, and incomplete replication (7, 98). Telomere erosion in a variety of cancers and cell lines has been found to lead to chromosome end associations that could contribute to genomic instability and gene amplification (18,47,60,82).It has been suggested that mammalian terminal (TTAGG G) n repeat arrays interact with the nuclear matrix (19, 44). Whether ATM gene effectors influence the interaction of telomeres with the nu...

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